Background: Neoadjuvant chemotherapy (NACT) is the standard early-stage triple-negative breast cancer (TNBC) treatment. Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. Younger patients have with poorer prognosis in breast cancer. To date, few studies are comparing the prognosis of AYA and older women (≥40) with breast cancer subtypes, specifically Triple-negative breast cancer (TNBC), as AYAs had higher proportions of this subtype. Method: Retrospective review was performed on female patients who received NACT at a King Hussien Cancer Center from January 2014 to June 2020. Data were collected from patients’ electronic medical records. TNBC was histopathologically confirmed. Logistic regression analysis of predictors of pathologic complete response (pCR). Survival curves were estimated with the Kaplan-Meier method. Multivariate analysis for EFS was performed using Cox’s proportional hazards regression model, covariates included age at diagnosis (AYA vs. ≥40), tumor size, nodal status LVI and pCR Result: We analyzed 211 women with stage I-III TNBC, including 62 (29.4%) women aged 18 to 39 years (AYA) and 149 (70.6%) ≥40 years. 138 (68.3%) were node positive, and 71 (34.8%) were T3/4 disease. Median follow-up was 28.1 months, median number of ER visit during NAC is 1 (0-11), 23 (10.9 %) patients had admission during neoadjuvant chemotherapy, most commonly due to febrile neutropenia 13 (56.9%). 37 (17.5%) patients did not complete NAC, due to disease progression in 22 (10.4%), and toxicity in 15 (7.1%) patients. 195 (92.4%) patients had surgery, including 75 (35.5%) had breast-conserving surgery (BCS). 166 (76.3%) patients had objective response, and 64 (30.3%) had pCR. 170 (80.6%) received adjuvant radiotherapy, and 38 (18%) received adjuvant capecitabine. No significant differences between the AYA and the ≥40 group in terms of clinicopathological, toxicity, pCR rate, and the rate of BCS. In univariate analysis, the LVI, nodal status, pCR, and age group were significant predictors of DFS. In multivariate analysis, only PCR and age are the only independent predictor of DFS. The median DFS was worse in the AYA population 47.8 (31.21-64.39) months vs. NR in ≥40 (p-value 0.013). In patients who achieved pCR, the estimated 5-years DFS for the AYA group was 56.1% versus 86.8% for the ≥40 group, (p-value 0.71). In patients with residual disease, PFS for AYA was 34.2 (95%CI 11.5-57) months vs. 59.5 months in the ≥40 group, (p 0.009). Conclusion: Although there is no difference in pCR between the AYA age group patient treated with NACT for TNBC and the older age group, the DFS is significantly worse in the AYA than the ≥40 age group in patients with residual disease. As well, DFS is numerically worse in the AYA age vs. the ≥40 age group in patients who achieved pCR. Citation Format: Faris Tamimi, Baha’ Sharaf, Suhaib Khater, Suhaib Al-Sawajneh, Malek Horani, Khalid M. Elrabii, Anas Zayed, Hikmat Abdel-Razeq. Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-06.

Background: Accounting for almost 20% of all cancer cases, breast cancer continues to be the most common cancer and the leading cause of cancer-related deaths among females. In our region, almost 50% of breast cancer patients are diagnosed at age 50 or younger. Around 5-15% of breast cancers are hereditary and mostly related to BRCA1 or BRCA2 gene mutations. Risk-reducing interventions, like bilateral mastectomies and oophorectomies, are highly recommended for carriers of pathogenic variants. More recently, data had shown that specific breast cancer treatment may be informed by BRCA1 or BRCA2 mutation status. Until very recently, genetic testing and genetic counseling services were prohibitively expensive and were not available or routinely offered. Given the recently identified high prevalence of pathogenic variants among our patients, and the wider availability and the lower cost of genetic testing, an opportunity exists to look back and offer such patients the chance to do genetic testing. Patients with positive tests can then be counseled, along with their close family members, for appropriate risk-reducing programs. Methods: Using our hospital-based cancer registry, we identified patients with breast cancer who fulfilled at least one of 3 approved indications for genetic testing but never had it. Eligible patients were those diagnosed at age 45 or younger, patients with triple-negative (TN) disease diagnosed at age 65 years or younger, and those with close blood relatives with breast or ovarian cancers. Patients were initially contacted over the phone and then seen by one of the investigators in our genetic counseling clinics. Testing was performed using next-generation sequencing (NGS)-based multi-gene panel (MGP) on a peripheral blood sample at a referral lab. Results: A total of 377 eligible patients were identified. The median age (range) was 48 (31-75) years. Genetic testing was performed on 198 (52.5%) and results were reported on 192. Age ≤45 years (n= 157, 79.3%) and TN-disease (n= 59, 29.8%) were the most common indications for testing. In total, 20 (10.4%) patients were found to have pathogenic/likely pathogenic variants; mostly in BRCA2 (n=9) and BRCA1 (n=7). An additional 4 patients had TP53, PALB2, and ATM. Variants of uncertain significance (VUS) were identified in 53 (27.6%) patients. Following the visit to the genetic counseling clinic, an additional 41 (22.9%) patients agreed to test. The remaining 136 (36.1%) failed to be tested because of lack of updated contact information (n=54, 39.7%), living outside the country (n=19, 14.0%) or lack of insurance coverage (n=36, 26.5%). Fear of social stigma, lack of interest, or emotional stress were the reason for refusal among 24 (17.6%) patients. Conclusions: The Traceback approach may provide an opportunity to diagnose pathogenic/likely pathogenic variants among previously diagnosed patients with breast cancer. The high percentage of patients couldn’t be tested for manageable reasons while fear of social stigma and emotional stress continued to be important barriers, especially in societies like ours. Given the important implications of genetic testing and its availability and affordability, reaching out to untested high-risk patients raises an ethical and professional dilemma that needs to be addressed from the physician, patients, and insurance perspectives. Citation Format: Faris Tamimi, Baha’ sharaf, Osama Salama, Sarah Edaily, Suhaib Khater, Mais AlKyam, Lama Abujamous, Khansa Azzam, Hala Abu-Fares, Haneen Abaza, Hikmat Abdel-Razeq. Challenges and Dilemmas Following a Traceback Approach for Genetic Counseling and Genetic Testing for Pathogenic Germline Mutations among High-Risk Patients Previously Diagnosed with Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-02.

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